. The objective of this project is to continue examination of the processes of blood coagulation and related phenomena with an increasing emphasis on the regulatory role of blood cells and endothelial cells. Our focus will be on regulation of the initial steps of clotting via the intrinsic pathway of thrombin formation, particularly upon control of the activation of Hageman factor (factor XII). Our immediate goal is to elucidate the role of inhibitors of the activation of this clotting factor that are derived from vascular endothelial cells. We will also explore the importance of metallic ions in activation of Hageman factor. These and related projects aim at an understanding of hemorrhagic and thrombolytic states. As always, vigorous attempts will be made to learn more about the physiology of hemostasis and thrombosis through study of suitable patients.